Synthetic Coordination Chemistry: Principles and Practice

Davies, J A; Hockensmith, C M; Kukushkin, V Yu; Kukushkin, Y N

doi:10.1142/9789812831378

Cited by 16 publications

(6 citation statements)

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“…Taking into account our previous experience in carrying out chemical transformations by exploring Anderson rearrangements, 34 complexes 1c , 1t , 2c , 2t , 3c , and 4c were synthesized by heating (H 2 azole) 2 [RuCl 5 (NO)], where Hazole = 1 H -indazole, 1 H -pyrazole, 1 H -benzimidazole, 1 H -imidazole in 1-propanol at 70–75 °C for 6–17 h. Separation of cis- and trans-isomers of (H 2 ind)[RuCl 4 (NO)(Hind)] (compounds 1c and 1t , respectively) was realized by fractional crystallization in chloroform. The less soluble trans-isomer 1t crystallized first, and the more soluble cis-isomer 1c thereafter.…”

Section: Resultsmentioning

confidence: 99%

Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles

et al. 2013

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Ruthenium nitrosyl complexes of the general formulas (cation)+[cis-RuCl4(NO)(Hazole)]−, where (cation)+ = (H2ind)+, Hazole = 1H-indazole (Hind) (1c), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (Hpz) (2c), (cation)+ = (H2bzim)+, Hazole = 1H-benzimidazole (Hbzim) (3c), (cation)+ = (H2im)+, Hazole = 1H-imidazole (Him) (4c) and (cation)+[trans-RuCl4(NO)(Hazole)]−, where (cation)+ = (H2ind)+, Hazole = 1H-indazole (1t), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (2t), as well as osmium analogues of the general formulas (cation)+[cis-OsCl4(NO)(Hazole)]−, where (cation)+ = (n-Bu4N)+, Hazole =1H-indazole (5c), 1H-pyrazole (6c), 1H-benzimidazole (7c), 1H-imidazole (8c), (cation)+ = Na+; Hazole =1H-indazole (9c), 1H-benzimidazole (10c), (cation)+ = (H2ind)+, Hazole = 1H-indazole (11c), (cation)+ = H2pz+, Hazole = 1H-pyrazole (12c), (cation)+ = (H2im)+, Hazole = 1H-imidazole (13c), and (cation)+[trans-OsCl4(NO)(Hazole)]−, where (cation)+ = n-Bu4N+, Hazole = 1H-indazole (5t), 1H-pyrazole (6t), (cation)+ = Na+, Hazole = 1H-indazole (9t), (cation)+ = (H2ind)+, Hazole = 1H-indazole (11t), (cation)+ = (H2pz)+, Hazole = 1H-pyrazole (12t), have been synthesized. The compounds have been comprehensively characterized by elemental analysis, ESI mass spectrometry, spectroscopic techniques (IR, UV–vis, 1D and 2D NMR) and X-ray crystallography (1c·CHCl3, 1t·CHCl3, 2t, 3c, 6c, 6t, 8c). The antiproliferative activity of water-soluble compounds (1c, 1t, 3c, 4c and 9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c) in the human cancer cell lines A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon adenocarcinoma) has been assayed. The effects of metal (Ru vs Os), cis/trans isomerism, and azole heterocycle identity on cytotoxic potency and cell line selectivity have been elucidated. Ruthenium complexes (1c, 1t, 3c, and 4c) yielded IC50 values in the low micromolar concentration range. In contrast to most pairs of analogous ruthenium and osmium complexes known, they turned out to be considerably more cytotoxic than chemically related osmium complexes (9c, 9t, 10c, 11c, 11t, 12c, 12t, 13c). The IC50 values of Os/Ru homologs differ by factors (Os/Ru) of up to ∼110 and ∼410 in CH1 and SW480 cells, respectively. ESI-MS studies revealed that ascorbic acid may activate the ruthenium complexes leading to hydrolysis of one M–Cl bond, whereas the osmium analogues tend to be inert. The interaction with myoglobin suggests nonselective adduct formation; i.e., proteins may act as carriers for these compounds.

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Section: Resultsmentioning

confidence: 99%

Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles

et al. 2013

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“…Quite recently, Anderson type rearrangement reactions(11) of (H 2 azole) 2 [Os IV Cl 6 ] in alcohols in the presence of tetrabutylammonium chloride enabled the synthesis of the next family of compounds, namely, ( n -Bu 4 N)[Os IV Cl 5 (Hazole)], where Hazole = 1 H -pyrazole, 1 H -indazole, 1 H -imidazole, 1 H -benzimidazole, or 1 H ,2,4-triazole. (5) The ( n -Bu 4 N) + was also substituted by biologically relevant or nontoxic cations such as Na + and (H 2 azole) + .…”

Section: Introductionmentioning

confidence: 99%

En Route to Osmium Analogues of KP1019: Synthesis, Structure, Spectroscopic Properties and Antiproliferative Activity of trans-[Os^IVCl₄(Hazole)₂]

et al. 2011

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By controlled Anderson type rearrangement reactions complexes of the general formula trans-[OsIVCl4(Hazole)2], where Hazole = 1H-pyrazole, 2H-indazole, 1H-imidazole, and 1H-benzimidazole, have been synthesized. Note that 2H-indazole tautomer stabilization in trans-[OsIVCl4(2H-indazole)2] is unprecedented in coordination chemistry of indazole. The metal ion in these compounds possesses the same coordination environment as ruthenium(III) in (H2ind)[RuIIICl4(Hind)2], where Hind = 1H-indazole, (KP1019), an investigational anticancer drug in phase I clinical trials. These osmium(IV) complexes are appropriate precursors for the synthesis of osmium(III) analogues of KP1019. In addition the formation of an adduct of trans-[OsIVCl4(Hpz)2] with cucurbit[7]uril is described. The compounds have been comprehensively characterized by elemental analysis, EI and ESI mass spectrometry, spectroscopy (IR, UV–vis, 1D and 2D NMR), cyclic voltammetry, and X-ray crystallography. Their antiproliferative acitivity in the human cancer cell lines CH1 (ovarian carcinoma), A549 (nonsmall cell lung carcinoma), and SW480 (colon carcinoma) is reported.

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“…The complex cis -[Os IV Cl 4 (κN2-1 H -ind) 2 ] ([ 1 ]) was prepared by Anderson rearrangement 56 in 1,1,2,2-tetrachloroethane at 128 °C starting from (H 2 ind)[Os IV Cl 5 (κN1-2 H -ind)]. This transformation is unprecedented in this family of compounds as it implies both a change of coordination mode from κN1 to κN2 of one indazole ligand and substitution of chlorido ligand by outer sphere indazole.…”

Section: Resultsmentioning

confidence: 99%

cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339

et al. 2017

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The relationship between cis-trans isomerism and anticancer activity has been mainly addressed for square-planar metal complexes, in particular, for platinum(II), e.g., cis- and trans-[PtCl2(NH3)2], and a number of related compounds, of which, however, only cis-counterparts are in clinical use today. For octahedral metal complexes, this effect of geometrical isomerism on anticancer activity has not been investigated systematically, mainly because the relevant isomers are still unavailable. An example of such an octahedral complex is trans-[RuCl4(Hind)2]−, which is in clinical trials now as its indazolium (KP1019) or sodium salt (NKP1339), but the corresponding cis-isomers remain inaccessible. We report the synthesis of Na[cis-OsIIICl4(κN2-1H-ind)2] (Na[1]) to show that cis-isomer of NKP1339 can in principle be prepared as well. The procedure involves heating (H2ind)[OsIVCl5(κN1-2H-ind)] in a high boiling point organic solvent resulting in an Anderson rearrangement with formation of cis-[OsIVCl4(κN2-1H-ind)2] ([1]) in high yield. The transformation is accompanied by an indazole coordination mode switch from κN1 to κN2 and stabilization of the 1H-indazole tautomer. Fully reversible spectroelectrochemical reduction of [1] in acetonitrile at 0.46 V vs NHE is accompanied by a change in electronic absorption bands indicating formation of cis-[OsIIICl4(κN2-1H-ind)2]− ([1]−). Chemical reduction of [1] in methanol with NaBH4 followed by addition of nBu4NCl afforded the osmium(III) complex nBu4N[cis-OsIIICl4(κN2-1H-ind)2] (nBu4N[1]). Metathesis reaction of nBu4N[1] with an ion exchange resin led to isolation of the water-soluble salt Na[1]. The X-ray diffraction crystal structure of [1]·Me2CO was determined and compared with that of trans-[OsIVCl4(κN2-1H-ind)]·2Me2SO (2·2Me2SO), also prepared in this work. EPR spectroscopy was performed on the OsIII complexes and the results analyzed by ligand-field and quantum chemical theories. We furthermore assayed effects of [1] and Na[1] on cell viability and proliferation in comparison to trans-[OsIVCl4(κN1-2H-ind)] [3] and cisplatin and found a strong reduction of cell viability at concentrations between 30 and 300 µM in different cancer cell lines (HT29, H446, 4T1 and HEK293). HT-29 cells are less sensitive to cisplatin than 4T1 cells, but more sensitive to [1] and Na[1], as shown by decreased proliferation and viability as well as an increased late apoptotic/necrotic cell population.

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Synthetic Coordination Chemistry: Principles and Practice

Cited by 16 publications

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Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles

Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles

En Route to Osmium Analogues of KP1019: Synthesis, Structure, Spectroscopic Properties and Antiproliferative Activity of trans-[Os^IVCl₄(Hazole)₂]

cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339

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Synthetic Coordination Chemistry: Principles and Practice

Cited by 16 publications

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Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles

Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles

En Route to Osmium Analogues of KP1019: Synthesis, Structure, Spectroscopic Properties and Antiproliferative Activity of trans-[OsIVCl4(Hazole)2]

cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339

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En Route to Osmium Analogues of KP1019: Synthesis, Structure, Spectroscopic Properties and Antiproliferative Activity of trans-[Os^IVCl₄(Hazole)₂]